Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency

Ashlee Conway, Fiona C Brown, Elinor J. Hortle, Gaetan Burgio, Simon J Foote, Craig James Morton, Stephen M. Jane, David J. Curtis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

In this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued.

Original languageEnglish
Article numberdmm034678
Number of pages8
JournalDisease Models and Mechanisms
Volume11
Issue number5
DOIs
Publication statusPublished - 21 May 2018

Keywords

  • Anaemia
  • Erythropoiesis
  • N-ethyl-N-nitrosourea
  • TPI deficiency
  • Transplantation

Cite this

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title = "Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency",
abstract = "In this study, we performed a genome-wide N-ethyl-N-nitrosourea (ENU) mutagenesis screen in mice to identify novel genes or alleles that regulate erythropoiesis. Here, we describe a recessive mouse strain, called RBC19, harbouring a point mutation within the housekeeping gene, Tpi1, which encodes the glycolysis enzyme, triosephosphate isomerase (TPI). A serine in place of a phenylalanine at amino acid 57 severely diminishes enzyme activity in red blood cells and other tissues, resulting in a macrocytic haemolytic phenotype in homozygous mice, which closely resembles human TPI deficiency. A rescue study was performed using bone marrow transplantation of wild-type donor cells, which restored all haematological parameters and increased red blood cell enzyme function to wild-type levels after 7 weeks. This is the first study performed in a mammalian model of TPI deficiency, demonstrating that the haematological phenotype can be rescued.",
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author = "Ashlee Conway and Brown, {Fiona C} and Hortle, {Elinor J.} and Gaetan Burgio and Foote, {Simon J} and Morton, {Craig James} and Jane, {Stephen M.} and Curtis, {David J.}",
year = "2018",
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doi = "10.1242/dmm.034678",
language = "English",
volume = "11",
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Bone marrow transplantation corrects haemolytic anaemia in a novel ENU mutagenesis mouse model of TPI deficiency. / Conway, Ashlee; Brown, Fiona C; Hortle, Elinor J.; Burgio, Gaetan; Foote, Simon J; Morton, Craig James; Jane, Stephen M.; Curtis, David J.

In: Disease Models and Mechanisms, Vol. 11, No. 5, dmm034678, 21.05.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Morton, Craig James

AU - Jane, Stephen M.

AU - Curtis, David J.

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